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Infliximab enhances the therapeutic effects of 5-fluorouracil resulting in tumor regression in colon cancer

Authors Liu F, Ai F, Tian L, Liu S, Zhao L, Wang X

Received 27 March 2016

Accepted for publication 7 June 2016

Published 3 October 2016 Volume 2016:9 Pages 5999—6008


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ram Prasad

Peer reviewer comments 2

Editor who approved publication: Dr William Cho

Fen Liu,1,2 Feiyan Ai,1,2 Li Tian,1 Shaojun Liu,1 Lian Zhao,1,2 Xiaoyan Wang1,2

1Department of Gastroenterology, The Third Xiangya Hospital of Central South University, 2Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, People’s Republic of China

Abstract: Colon cancer (CC) is among the most common malignant diseases with a dismal survival. Tumor necrosis factor-alpha (TNF-α) has been identified as a therapeutic target in various cancers, and anti-TNF-α treatment has shown promising effects in different cancer models. However, if TNF-α can be targeted in CC, the therapeutic values of anti-TNF-α treatment in CC remain unknown. Our study indicated that TNF-α is highly expressed in CC cell lines and patient tumor samples. High expression of TNF-α is an independent adverse prognosticator of CC. Targeting the TNF-α by its antibody infliximab induced antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity and enhanced apoptosis leading to cell death. The combination of infliximab with 5-fluorouracil showed better responses in vitro and in vivo than 5-fluorouracil alone. In conclusion, this study identified TNF-α as a target of CC and anti-TNF-α treatment synergized with chemotherapy leading to a better outcome in preclinical models.

Keywords: colon cancer, tumor necrosis factor-alpha, chemotherapy, prognosis, tumor regression

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